Difference between revisions of "Huai 2013 J Cell Sci"
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{{Publication | {{Publication | ||
|title=Huai J, Vögtle FN, Jöckel L, Li Y, Kiefer T, Ricci JE, Borner C (2013) TNFα-induced lysosomal membrane permeability (LMP) is downstream of MOMP and triggered by caspase-mediated p75 cleavage and ROS formation. J Cell Sci 126:4015- | |title=Huai J, Vögtle FN, Jöckel L, Li Y, Kiefer T, Ricci JE, Borner C (2013) TNFα-induced lysosomal membrane permeability (LMP) is downstream of MOMP and triggered by caspase-mediated p75 cleavage and ROS formation. J Cell Sci 126:4015-25. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/23788428 PMID: 23788428] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/23788428 PMID: 23788428] | ||
|authors=Huai J, | |authors=Huai J, Voegtle FN, Joeckel L, Li Y, Kiefer T, Ricci JE, Borner C | ||
|year=2013 | |year=2013 | ||
|journal=J Cell Sci | |journal=J Cell Sci | ||
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}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Genetic knockout;overexpression | |||
|injuries=Cell death | |||
|organism=Human, Mouse | |||
|tissues=HeLa, Fibroblast | |||
|preparations=Intact cells | |||
|couplingstates=ROUTINE | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 15:34, 9 November 2016
Huai J, Vögtle FN, Jöckel L, Li Y, Kiefer T, Ricci JE, Borner C (2013) TNFα-induced lysosomal membrane permeability (LMP) is downstream of MOMP and triggered by caspase-mediated p75 cleavage and ROS formation. J Cell Sci 126:4015-25. |
Huai J, Voegtle FN, Joeckel L, Li Y, Kiefer T, Ricci JE, Borner C (2013) J Cell Sci
Abstract: When NF-κB activation or protein synthesis is inhibited, tumor necrosis factor alpha (TNFα) can induce apoptosis through Bax- and Bak-mediated mitochondrial outer membrane permeabilization (MOMP) leading to caspase-3 activation. Additionally, previous studies have implicated lysosomal membrane permeability (LMP) and formation of reactive oxygen species (ROS) as early steps of TNFα-induced apoptosis. However, how these two events connect to MOMP and caspase-3 activation has been largely debated. Here, we present the novel finding that LMP induced by the addition of TNFα plus cycloheximide (CHX), the release of lysosomal cathepsins and ROS formation do not occur upstream but downstream of MOMP and require the caspase-3-mediated cleavage of the p75 NDUFS1 subunit of respiratory complex I. Both a caspase non-cleavable p75 mutant and the mitochondrially localized antioxidant MitoQ prevent LMP mediated by TNFα plus CHX and partially interfere with apoptosis induction. Moreover, LMP is completely blocked in cells deficient in both Bax and Bak, Apaf-1, caspase-9 or both caspase-3 and -7. Thus, after MOMP, active caspase-3 exerts a feedback action on complex I to produce ROS. ROS then provoke LMP, cathepsin release and further caspase activation to amplify TNFα apoptosis signaling. • Keywords: Apoptosis, Apoptosome, Bak, Bax, Caspase, LMP, MOMP, MitoQ, ROS, TNFα
Labels: MiParea: Respiration, Genetic knockout;overexpression
Stress:Cell death Organism: Human, Mouse Tissue;cell: HeLa, Fibroblast Preparation: Intact cells
Coupling state: ROUTINE
HRR: Oxygraph-2k